Biological impact assessment of nanomaterial used in nanomedicine. Introduction to the NanoTEST project.

Therapeutic nanoparticles (NPs) are used in nanomedicine as drug carriers or imaging agents, providing increased selectivity/specificity for diseased tissues. The first NPs in nanomedicine were developed for increasing the efficacy of known drugs displaying dose-limiting toxicity and poor bioavailability and for enhancing disease detection. Nanotechnologies have gained much interest owing to their huge potential for applications in industry and medicine. It is necessary to ensure and control the biocompatibility of the components of therapeutic NPs to guarantee that intrinsic toxicity does not overtake the benefits. In addition to monitoring their toxicity in vitro, in vivo and in silico, it is also necessary to understand their distribution in the human body, their biodegradation and excretion routes and dispersion in the environment. Therefore, a deep understanding of their interactions with living tissues and of their possible effects in the human (and animal) body is required for the safe use of nanoparticulate formulations. Obtaining this information was the main aim of the NanoTEST project, and the goals of the reports collected together in this special issue are to summarise the observations and results obtained by the participating research teams and to provide methodological tools for evaluating the biological impact of NPs.

Towards an alternative testing strategy for nanomaterials used in nanomedicine: Lessons from NanoTEST.

In spite of recent advances in describing the health outcomes of exposure to nanoparticles (NPs), it still remains unclear how exactly NPs interact with their cellular targets. Size, surface, mass, geometry, and composition may all play a beneficial role as well as causing toxicity. Concerns of scientists, politicians and the public about potential health hazards associated with NPs need to be answered. With the variety of exposure routes available, there is potential for NPs to reach every organ in the body but we know little about the impact this might have. The main objective of the FP7 NanoTEST project ( www.nanotest-fp7.eu ) was a better understanding of mechanisms of interactions of NPs employed in nanomedicine with cells, tissues and organs and to address critical issues relating to toxicity testing especially with respect to alternatives to tests on animals. Here we describe an approach towards alternative testing strategies for hazard and risk assessment of nanomaterials, highlighting the adaptation of standard methods demanded by the special physicochemical features of nanomaterials and bioavailability studies. The work has assessed a broad range of toxicity tests, cell models and NP types and concentrations taking into account the inherent impact of NP properties and the effects of changes in experimental conditions using well-characterized NPs. The results of the studies have been used to generate recommendations for a suitable and robust testing strategy which can be applied to new medical NPs as they are developed.

Testing a new multigroup inference approach to reconstructing past environmental conditions

A new, quantitative, inference model for environmental reconstruction (transfer function), based for the first time on the simultaneous analysis of multigroup species, has been developed. Quantitative reconstructions based on palaeoecological transfer functions provide a powerful tool for addressing questions of environmental change in a wide range of environments, from oceans to mountain lakes, and over a range of timescales, from decades to millions of years. Much progress has been made in the development of inferences based on multiple proxies but usually these have been considered separately, and the different numeric reconstructions compared and reconciled post-hoc. This paper presents a new method to combine information from multiple biological groups at the reconstruction stage. The aim of the multigroup work was to test the potential of the new approach to making improved inferences of past environmental change by improving upon current reconstruction methodologies. The taxonomic groups analysed include diatoms, chironomids and chrysophyte cysts. We test the new methodology using two cold-environment training-sets, namely mountain lakes from the Pyrenees and the Alps. The use of multiple groups, as opposed to single groupings, was only found to increase the reconstruction skill slightly, as measured by the root mean square error of prediction (leave-one-out cross-validation), in the case of alkalinity, dissolved inorganic carbon and altitude (a surrogate for air-temperature), but not for pH or dissolved CO2. Reasons why the improvement was less than might have been anticipated are discussed. These can include the different life-forms, environmental responses and reaction times of the groups under study.

Positive Outcomes Influence the Rate and Time to Publication, but Not the Impact Factor of Publications of Clinical Trial Results

Objectives: Publication bias may affect the validity of evidence based medical decisions. The aim of this study is to assess whether research outcomes affect the dissemination of clinical trial findings, in terms of rate, time to publication, and impact factor of journal publications. Methods and Findings: All drug-evaluating clinical trials submitted to and approved by a general hospital ethics committee between 1997 and 2004 were prospectively followed to analyze their fate and publication. Published articles were identified by searching Pubmed and other electronic databases. Clinical study final reports submitted to the ethics committee, final reports synopses available online and meeting abstracts were also considered as sources of study results. Study outcomes were classified as positive (when statistical significance favoring experimental drug was achieved), negative (when no statistical significance was achieved or it favored control drug) and descriptive (for non-controlled studies). Time to publication was defined as time from study closure to publication. A survival analysis was performed using a Cox regression model to analyze time to publication. Journal impact factors of identified publications were recorded. Publication rate was 48·4% (380/785). Study results were identified for 68·9% of all completed clinical trials (541/785). Publication rate was 84·9% (180/212) for studies with results classified as positive and 68·9% (128/186) for studies with results classified as negative (p<0·001). Median time to publication was 2·09 years (IC95 1·61-2·56) for studies with results classified as positive and 3·21 years (IC95 2·69-3·70) for studies with results classified as negative (hazard ratio 1·99 (IC95 1·55-2·55). No differences were found in publication impact factor between positive (median 6·308, interquartile range: 3·141-28·409) and negative result studies (median 8·266, interquartile range: 4·135-17·157). Conclusions: Clinical trials with positive outcomes have significantly higher rates and shorter times to publication than those with negative results. However, no differences have been found in terms of impact factor.

THE IMPACT OF ARCHITECTURAL DESIGN ON SOFTWARE DEVELOPMENT

Tässä työssä tutkitaan ohjelmistoarkkitehtuurisuunnitteluominaisuuksien vaikutusta erään client-server –arkkitehtuuriin perustuvan mobiilipalvelusovelluksen suunnittelu- ja toteutusaikaan. Kyseinen tutkimus perustuu reaalielämän projektiin, jonka kvalitatiivinen analyysi paljasti arkkitehtuurikompponenttien välisten kytkentöjen merkittävästi vaikuttavan projektin työmäärään. Työn päätavoite oli kvantitatiivisesti tutkia yllä mainitun havainnon oikeellisuus. Tavoitteen saavuttamiseksi suunniteltiin ohjelmistoarkkitehtuurisuunnittelun mittaristo kuvaamaan kyseisen järjestelmän alijärjestelmien arkkitehtuuria ja luotiin kaksi suunniteltua mittaristoa käyttävää, työmäärää (komponentin suunnittelu-, toteutus- ja testausaikojen summa) arvioivaa mallia, joista toinen on lineaarinen ja toinen epälineaarinen. Näiden mallien kertoimet sovitettiin optimoimalla niiden arvot epälineaarista gloobaalioptimointimenetelmää, differentiaalievoluutioalgoritmia, käyttäen, niin että mallien antamat arvot vastasivat parhaiten mitattua työmäärää sekä kaikilla ominaisuuksilla eli attribuuteilla että vain osalla niistä (yksi jätettiin vuorotellen pois). Kun arkkitehtuurikompenttien väliset kytkennät jätettiin malleista pois, mitattujen ja arvoitujen työmäärien välinen ero (ilmaistuna virheenä) kasvoi eräässä tapauksessa 367 % entisestä tarkoittaen sitä, että näin muodostettu malli vastasi toteutusaikoja huonosti annetulla ainestolla. Tämä oli suurin havaitu virhe kaikkien poisjätettyjen ominaisuuksien kesken. Saadun tuloksen perusteella päätettiin, että kyseisen järjestelmän toteutusajat ovat vahvasti riippuvaisia kytkentöjen määrästä, ja näin ollen kytkentöjen määrä oli mitä todennäköisemmin kaikista tärkein työmäärään vaikuttava tekijä tutkitun järjestelmän arkkitehtuurisuunnittelussa.

Preparation of a blood culture pellet for rapid bacterial identification and antibiotic susceptibility testing.

Bloodstream infections and sepsis are a major cause of morbidity and mortality. The successful outcome of patients suffering from bacteremia depends on a rapid identification of the infectious agent to guide optimal antibiotic treatment. The analysis of Gram stains from positive blood culture can be rapidly conducted and already significantly impact the antibiotic regimen. However, the accurate identification of the infectious agent is still required to establish the optimal targeted treatment. We present here a simple and fast bacterial pellet preparation from a positive blood culture that can be used as a sample for several essential downstream applications such as identification by MALDI-TOF MS, antibiotic susceptibility testing (AST) by disc diffusion assay or automated AST systems and by automated PCR-based diagnostic testing. The performance of these different identification and AST systems applied directly on the blood culture bacterial pellets is very similar to the performance normally obtained from isolated colonies grown on agar plates. Compared to conventional approaches, the rapid acquisition of a bacterial pellet significantly reduces the time to report both identification and AST. Thus, following blood culture positivity, identification by MALDI-TOF can be reported within less than 1 hr whereas results of AST by automated AST systems or disc diffusion assays within 8 to 18 hr, respectively. Similarly, the results of a rapid PCR-based assay can be communicated to the clinicians less than 2 hr following the report of a bacteremia. Together, these results demonstrate that the rapid preparation of a blood culture bacterial pellet has a significant impact on the identification and AST turnaround time and thus on the successful outcome of patients suffering from bloodstream infections.

Frequency of fear of needles and impact of a multidisciplinary educational approach towards pregnant women with diabetes

PURPOSE: To evaluate the frequency of fear of needles and the impact of a multidisciplinary educational program in women with pre-gestational and gestational diabetes taking insulin during pregnancy. METHODS: The short Diabetes Fear of Injecting and Self-testing Questionnaire (D-FISQ), composed by two subscales that access fear of self injection (FSI) and fear of self testing (FST), was administered twice during pregnancy to 65 pregnant women with pre-gestational and gestational diabetes: at the first endocrine consult and within the last two weeks of pregnancy or postpartum. An organized multidisciplinary program provided diabetes education during pregnancy. Statistical analysis was carried out by Wilcoxon and McNemar tests and Spearman correlation. A p<0.05 was considered to be significant. RESULTS: Data from the short D-FISQ questionnaire shows that 43.1% of pregnant women were afraid of needles in the first evaluation. There was a significant reduction in scores for FSI and FST subscales between the first and second assessments (first FSI 38.5% compared with second 12.7%, p=0.001; first FST 27.7% compared with second FST 14.3%, p=0.012). CONCLUSIONS: The fear of needles is common in pregnant women on insulin therapy and an organized multidisciplinary educational diabetes program applied during pregnancy reduces scores of such fear.

Testing FCM technique for the wind energy scenarios in Finland

In the latter days, human activities constantly increase greenhouse gases emissions in the atmosphere, which has a direct impact on a global climate warming. Finland as European Union member, developed national structural plan to promote renewable energy generation, pursuing the aspects of Directive 2009/28/EC and put it on the sharepoint. Finland is on a way of enhancing national security of energy supply, increasing diversity of the energy mix. There are plenty significant objectives to develop onshore and offshore wind energy generation in country for a next few decades, as well as another renewable energy sources. To predict the future changes, there are a lot of scenario methods developed and adapted to energy industry. The Master’s thesis explored “Fuzzy cognitive maps” approach in scenarios developing, which captures expert’s knowledge in a graphical manner and using these captures for a raw scenarios testing and refinement. There were prospects of Finnish wind energy development for the year of 2030 considered, with aid of FCM technique. Five positive raw scenarios were developed and three of them tested against integrated expert’s map of knowledge, using graphical simulation. The study provides robust scenarios out of the preliminary defined, as outcome, assuming the impact of results, taken after simulation. The thesis was conducted in such way, that there will be possibilities to use existing knowledge captures from expert panel, to test and deploy different sets of scenarios regarding to Finnish wind energy development.

Testing Accrual-Based Model for Detecting Earnings Management: Comparison of Finland and France

The aim of this study is to test the accrual-based model suggested by Dechow et al. (1995) in order to detect and compare earnings management practices in Finnish and French companies. Also the impact of financial crisis of 2008 on earnings management behavior in these countries is tested by dividing the whole time period of 2003-2012 into two sub-periods: pre-crisis (2003-2008) and post-crisis (2009-2012). Results support the idea that companies in both countries have significant earnings management practices. During the post-crisis period companies in Finland show income inflating practices, while in France the opposite tendency is noticed (income deflating) during the same period. Results of the assumption that managers in highly concentrated companies are engaged in income enhancing practices vary in two countries. While in Finland managers are trying to show better performance for bonuses or other contractual compensation motivations, in France they avoid paying dividends or high taxes.

Evaluating land-use related environmental impacts of biomass value chains for decision-support : Comparison and testing of methodologies proposed for environmental life cycle assessment

Life cycle assessment (LCA) is one of the most established quantitative tools for environmental impact assessment of products. To be able to provide support to environmentally-aware decision makers on environmental impacts of biomass value-chains, the scope of LCA methodology needs to be augmented to cover landuse related environmental impacts. This dissertation focuses on analysing and discussing potential impact assessment methods, conceptual models and environmental indicators that have been proposed to be implemented into the LCA framework for impacts of land use. The applicability of proposed indicators and impact assessment frameworks is tested from practitioners' perspective, especially focusing on forest biomass value chains. The impacts of land use on biodiversity, resource depletion, climate change and other ecosystem services is analysed and discussed and the interplay in between value choices in LCA modelling and the decision-making situations to be supported is critically discussed. It was found out that land use impact indicators are necessary in LCA in highlighting differences in impacts from distinct land use classes. However, many open questions remain on certainty of highlighting actual impacts of land use, especially regarding impacts of managed forest land use on biodiversity and ecosystem services such as water regulation and purification. The climate impact of energy use of boreal stemwood was found to be higher in the short term and lower in the long-term in comparison with fossil fuels that emit identical amount of CO2 in combustion, due to changes implied to forest C stocks. The climate impacts of energy use of boreal stemwood were found to be higher than the previous estimates suggest on forest residues and stumps. The product lifetime was found to have much higher influence on the climate impacts of woodbased value chains than the origin of stemwood either from thinnings or final fellings. Climate neutrality seems to be likely only in the case when almost all the carbon of harvested wood is stored in long-lived wooden products. In the current form, the land use impacts cannot be modelled with a high degree of certainty nor communicated with adequate level of clarity to decision makers. The academia needs to keep on improving the modelling framework, and more importantly, clearly communicate to decision-makers the limited certainty on whether land-use intensive activities can help in meeting the strict mitigation targets we are globally facing.

Impact of acute exposure to air pollution on the cardiorespiratory performance of military firemen

The objective of the present study was to determine the impact of acute short-term exposure to air pollution on the cardiorespiratory performance of military fireman living and working in the city of Guarujá, São Paulo, Brazil. Twenty-five healthy non-smoking firemen aged 24 to 45 years had about 1 h of exposure to low and high levels of air pollution. The tests consisted of two phases: phase A, in Bertioga, a town with low levels of air pollution, and phase B, in Cubatão, a polluted town, with a 7-day interval between phases. The volunteers remained in the cities (Bertioga/Cubatão) only for the time required to perform the tests. Cumulative load 10 ± 2 min-long exertion tests were performed on a treadmill, consisting of a 2-min stage at a load of 7 km/h, followed by increasing exertion of 1 km h-1 min-1 until the maximum individual limit. There were statistically significant differences (P < 0.05) in anaerobic threshold (AT) between Cubatão (35.04 ± 4.91 mL kg-1 min-1) and Bertioga (36.98 ± 5.62 mL kg-1 min-1; P = 0.01), in the heart rate at AT (AT HR; Cubatão 152.08 ± 14.86 bpm, Bertioga 157.44 ± 13.64 bpm; P = 0.001), and in percent maximal oxygen consumption at AT (AT%VO2max; Cubatão 64.56 ± 6.55%, Bertioga 67.40 ± 5.35%; P = 0.03). However, there were no differences in VO2max, maximal heart rate or velocity at AT (ATvel) observed in firemen between towns. The acute exposure to pollutants in Cubatão, SP, caused a significant reduction in the performance at submaximal levels of physical exertion.

Impact of Word-of-Mouth on consumer decision-making: An information processing perspective in the context of a high-involvement service

This doctoral study conducts an empirical analysis of the impact of Word-of-Mouth (WOM) on marketing-relevant outcomes such as attitudes and consumer choice, during a high-involvement and complex service decision. Due to its importance to decisionmaking, WOM has attracted interest from academia and practitioners for decades. Consumers are known to discuss products and services with one another. These discussions help consumers to form an evaluative opinion, as WOM reduces perceived risk, simplifies complexity, and increases the confidence of consumers in decisionmaking. These discussions are also highly impactful as WOM is a trustworthy source of information, since it is independent from the company or brand. In responding to the calls for more research on what happens after WOM information is received, and how it affects marketing-relevant outcomes, this dissertation extends prior WOM literature by investigating how consumers process information in a highinvolvement service domain, in particular higher-education. Further, the dissertation studies how the form of WOM influences consumer choice. The research contributes to WOM and services marketing literature by developing and empirically testing a framework for information processing and studying the long-term effects of WOM. The results of the dissertation are presented in five research publications. The publications are based on longitudinal data. The research leads to the development of a proposed theoretical framework for the processing of WOM, based on theories from social psychology. The framework is specifically focused on service decisions, as it takes into account evaluation difficulty through the complex nature of choice criteria associated with service purchase decisions. Further, other gaps in current WOM literature are taken into account by, for example, examining how the source of WOM and service values affects the processing mechanism. The research also provides implications for managers aiming to trigger favorable WOM through marketing efforts, such as advertising and testimonials. The results provide suggestions on how to design these marketing efforts by taking into account the mechanism through which information is processed, or the form of social influence.

The impact of scheduling on the implementation of the new Ontario curriculum: teachers' perceptions /

This qualitative study explored secondary teachers' perceptions of scheduling in relation to pedagogy, curriculum, and observation of student learning. Its objective was to determine the best way to organize the scheduling for the delivery of Ontario's new 4-year curriculum. Six participants were chosen. Two were teaching in a semestered timetable, 1 in a traditional timetable, and 3 had experience in both schedules. Participants related a pressure cooker "lived experience" with weaker students in the semester system experiencing a particularly harsh environment. The inadequate amount of time for review in content-heavy courses, gap scheduling problems, catch-up difficulties for students missing classes, and the fast pace of semestering are identified as factors negatively impacting on these students. Government testing adds to the pressure by shifting teachers' time and attention in the classroom from deeper learning to a superficial coverage of material, from curriculum as lived to curriculum as text to be covered. Scheduling choice should be available in public education to accommodate the needs of all students. Curriculum guidelines need to be revamped to reflect the content that teachers believe is necessary for a successful course delivery. Applied level courses need to be developed for students who are not academically inferior but learn differently.

The impact of the Canadian Standardized Test of Fitness and of health counselling on health attitudes and behaviour

The purpose of this research study was to determine whether or not the use of a single day of Personal Wellness Evaluations would be meaningful enough to change the attitudes of participants toward adopting a healthier lifestyle, or if it was necessary to include regular planned health counselling alon-g with the Personal Wellness Evaluations in order to'observe changes in beliefs, attitudes and behaviours toward active living and the adoption of a healthier lifestyle. Attitudes and behaviours toward physical fitness and healthy lifestyle choices were assessed through a questionnaire composed of the following instruments: Fishbein and Ajzen Attitude and Behaviour Questionnaire, Leisure Behaviour Questionnaire, Ten Centimeter Bipolar Health Continuum, Neugarten Life Satisfaction Assessment, Job Description Index, Selected questions from the Ontario Health Survey, and the Symptom Reporting Questionnaire. Physical fitness evaluation consisted of the Canadian Standardized Test of Fitness, measures of blood pressure, and total cholesterol. The participants were divided into three groups: Group 1- CSTF & health counselling, Group 2- CSTF only, and Group 3- a control group. All three groups received the questionnaire both at the beginning and at the end of the study. Group 1 and Group 2 also participated in fitness testing at these same times, with a three-month time interval between test times. Group 1 also received weekly one-hour health education sessions during the three months between fitness testing. While there were some differences found between the three groups in this study, the results of this study suggested that this three-month workplace wellness program had no impact on the participants' attitudes and behaviours toward health and physical activity. There were no significant differences in the physical fitness measures between Group 1 and Group 2 , nor in the participants' questionnaire responses. These results may be due to the participants' lack of compliance to this wellness program. Employees who 11 participate in a workplace weIlness program must be self-motivated to comply with the program in order to receive the full benefits the program has to offer. Some participants in this study did not have the internal motivation necessary to remain in the study for the three-month period. Future research may consider implementing a workplace wellness program for a longer duration as well as incorporating a specific physical fitness program for the participants to follow. An exercise program could improve the participants' physical fitness, while the health counselling would give the individuals the health education necessary to lead a healthy lifestyle.

Globalization and Its Impact on Assessment: Moving Toward a New Story

Globalization has resulted in large-scale international and local assessments closely tied to notions of accountability and competitiveness in a globalized economy. Although policy makers seek to ensure citizens meet the demands of a global knowledge-based economy, such assessments may also impede the development of requisite 21st century skills. While standardization currently is viewed as the most effective measurement of student achievement, several Canadian and international jurisdictions are moving toward assessment for learning (AfL). This conceptual study sought to identify whether AfL or standardized assessment most effectively meets 21st century learning goals in the wake of rapid global change. It applies a Story Model theoretical framework to understand the current, the new emerging, and the future ideal story of education from a personal, cultural, and global lens. The study examines the main critiques and/or challenges of standardized testing, the benefits of AfL for student learning, and new teaching and assessment approaches to the development of 21st century learning goals. The study applies the Story Model’s inside-outside/past-future approach to determine the future direction of assessment. Results show that the new story of assessment will most likely entail a model that integrates both standardized testing and in-class assessments in the form of AfL and PBL.